Mirapex
Mirapex - General Information
Mirapex (INN, trade names Mirapex® and Sifrol®) is a medication indicated for treating Parkinson's disease and restless legs syndrome (RLS). It is also sometimes used off-label as a treatment for cluster headache or to counteract the problems with low libido experienced by some users of SSRI antidepressant drugs. Mirapex has shown robust effects on pilot studies in bipolar disorder. Mirapex is classified as a non-ergoline dopamine agonist.
Pharmacology of Mirapex
Mirapex is a nonergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. The relevance of D3 receptor binding in Parkinson's disease is unknown. The precise mechanism of action of Mirapex as a treatment for Parkinson's disease is unknown, although it is believed to be related to its ability to stimulate dopamine receptors in the striatum. This conclusion is supported by electrophysiologic studies in animals that have demonstrated that Mirapex influences striatal neuronal firing rates via activation of dopamine receptors in the striatum and the substantia nigra, the site of neurons that send projections to the striatum.
Mirapex for patients
Patients should be instructed to take MIRAPEX only as prescribed.
Patients should be informed that hallucinations can occur and that the elderly are at a higher risk than younger patients with Parkinson 's disease.
Patients may develop postural (orthostatic) hypotension, with or without symptoms such as dizziness, nausea, fainting or blackouts, and sometimes, sweating. Hypotension may occur more frequently during initial therapy. Accordingly, patients should be cautioned against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods and especially at the initiation of treatment with MIRAPEX.
Patients should be advised that MIRAPEX may cause somnolence and that they should neither drive a car nor operate other complex machinery until they have gained sufficient experience on MIRAPEX to gauge whether or not it affects their mental and/or motor performance adversely. Because of the possible additive sedative effects, caution should also be used when patients are taking other CNS depressants in combination with MIRAPEX.
Because the teratogenic, potential of pramipexole has not been completely established in laboratory animals, and because experience in humans is limited, patients should be advised to notify their physicians if they become pregnant or intend to become pregnant during therapy.
Because of the possibility that pramipexole may be excreted in breast milk, patients should be advised to notify their physicians if they intend to breast-feed or are breast-feeding an infant.
If patients develop nausea, they should be advised that taking MIRAPEX with food may reduce the occurrence of nausea.
Mirapex Interactions
Carbidopa/Levodopa: Carbidopa/Levodopa does not influence the pharmacokinetics of pramipexole in healthy volunteers (N= 10). Pramipexole did not alter the extent of absorption (AUC) or the elimination of carbidopa/ levodopa, although it caused an increase in levodopa Cmax by about 40% and a decrease in Tmax from 2.5 to 0. 5 hours.
Selegiline: In healthy volunteers (N= 11), selegiline did not influence the pharmacokinetics of pramipexole.
Amantadine: Population pharmacokinetic analysis suggests that amantadine is unlikely to alter the oral clearance of pramipexole (N= 54).
Cimetidine: Cimetidine, a known inhibitor of renal tubular secretion of organic bases via the cationic transport system, caused a 50% increase in pramipexole AUC and a 40% increase in half-life (N= 12).
Probenecid: Probenecid, a known inhibitor of renal tubular secretion of organic acids via the aruonic transporter, did not noticeably influence pramipexole pharmacokinetics (N= 12).
Other drugs eliminated via renal secretion: Population pharmacokinetic analysis suggests that coadministration of drugs that are secreted by the cationic transport system (e.g., cimetidine, ranitidine, diltiazem, triamterene, verapamil, quinidine, and quinine) decreases the oral clearance of pramipexole by about 20%, while those secreted by the anionic transport system (e.g., cephalosporins, penicillins, indomethacin, hydrochlorothiazide, and chlorpropamide) are likely to have little effect on the oral clearance of pramipexole.
CYP interactions: Inhibitors of cytochrome P450 enzymes would not be expected to affect pramipexole elimination because pramipexole is not appreciably metabolized by these enzymes in vivo or in vitro. Pramipexole does not inhibit CYP enzymes CYPIA2, CYP2C9, CYP2CI9, CYP2EI, and CYP3A4. Inhibition of CYP2D6 was observed with an apparent Ki of 30 uM, indicating that pramipexole will not inhibit CYP enzymes at plasma concentrations observed following the highest recommended clinical dose (1.5 mg tid).
Dopamine antagonists: Since pramipexole is a dopamine agonist, it is possible that dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of MIRAPEX.
Drug/ Laboratory Test Interactions
There are no known interactions between MIRAPEX and laboratory tests.
Mirapex Contraindications
MIRAPEX Tablets are contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.
Additional information about Mirapex
Mirapex Indication: For the treatment of signs and symptoms of idiopathic Parkinson's disease
Mechanism Of Action: The precise mechanism of action of Mirapex as a treatment for Parkinson's disease is unknown, although it is believed to be related to its ability to stimulate dopamine receptors in the striatum.
Drug Interactions: Cimetidine Cimetidine increases the effect and toxicity of pramipexole
Food Interactions: Not Available
Generic Name: Pramipexole
Synonyms: Furfuryl Acetate; Pramipexol [Spanish]; Pramipexole 2HCl Monohydrate; Pramipexole hydrochloride; Pramipexolum [Latin]; Pramipexol
Drug Category: Free Radical Scavengers; Antiparkinson Agents; Antidyskinetics; Antioxidants
Drug Type: Small Molecule; Approved
Other Brand Names containing Pramipexole: Mirapex;
Absorption: Rapid. Absolute bioavailability is greater than 90%, indicating that pramipexole is well absorbed and undergoes little presystemic metabolism. Food does not affect the extent of absorption.
Toxicity (Overdose): Not Available
Protein Binding: About 15% bound to plasma proteins.
Biotransformation: No metabolites have been identified in plasma or urine.
Half Life: 8 hours
Dosage Forms of Mirapex: Tablet Oral
Chemical IUPAC Name: (6R)-N'-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
Chemical Formula: C10H17N3S
Pramipexole on Wikipedia: https://en.wikipedia.org/wiki/Pramipexole
Organisms Affected: Humans and other mammals
